This proposal outlines the three year research plan in a first independent position as an Assistant Professor in epidemiology at the College of Public Health at the Ohio State University. This proposal bridges basic science and epidemiological research, a long-term career goal. The research of this proposal focuses on early-onset obesity and the risk of colon cancer. This is an important area of research because of the increasing trend of obesity in the United States with 70% of all American adults and 30% of children currently defined as overweight or obese. The hypothesis is that early-onset obesity contributes to colon carcinogenesis through alterations in the IGF-1 and inflammatory pathways. The specific aims of this proposal are: 1) identify the impact of early-onset obesity on colon tumorigenesis in mice and 2) determine the longitudinal effect of obesity on colon cancer risk in humans. Specific aim 1 will be accomplished using a mouse model of early-onset diet-induced obesity. Mice will be fed: 1) a high fat diet early during their development to induced obesity;2) a high fat diet during adulthood to induce obesity;or 3) a control diet throughout their development. All mice will be administered a colon cancer carcinogen and monitored for colon cancer. At the end of the study, colon tumor development will be assessed along with examination of pathways that are potentially. These pathways include inflammation and insulin-like growth factor-1. The effect of early-onset obesity will be compared to adult-onset and the control group. Specific aim 2 will be investigated using two different human populations. First, the Women's Health Initiative (WHI) will be used to examine how body mass index (BMI) starting at age 18 and continuing through the lifespan is associated with colon cancer risk. Blood specimens from this cohort will be used to examine the same biomarkers that are investigated in the animal study to examine the relevance of our mouse model to the human population. Secondly, data from the Danish registry will be utilized to examine how BMI starting during early childhood and continuing through adulthood is associated with colon cancer risk. This will be the first proposal to use both animal and human cohorts to investigate the long-term consequences of childhood obesity on colon cancer. Furthermore, the proposed research will allow the Principal Investigator to expand her training in epidemiology and as well as in childhood obesity and colon cancer. It is anticipated that data obtained from both the mouse model as well as the human cohorts will be used to develop an R01 that will further investigate the effect of early-onset obesity on colon cancer. The transdisciplinary nature of this application could lead to characterizing and testing obesity-related biomarkers in human studies. This proposal has direct relevance to the mission of the National Cancer Institute in understanding both the cause, and potential ways to prevent, obesity-promoted colon cancer. PUBLIC HEALTH RELEVANCE: Obesity is an enormous public health concern with over 70% of American adults and 30% of children considered overweight or obese. There are many long-term health effects of obesity, however, the impact of early-onset obesity on cancer risk is uncertain. This proposal will examine the impact of early-onset obesity on colon cancer risk and the molecular mechanisms underlying these effects. The written critiques and criteria scores of individual reviewers are provided in essentially unedited form in the "Critique" section below. Please note that these critiques and criteria scores were prepared prior to the meeting and may not have been revised subsequent to any discussions at the review meeting. The "Resume and Summary of Discussion" section above summarizes the final opinions of the committee.